As the number of persons infected with Human Immunodeficiency Virus (HIV) reaches 2 million in the United States, there is a growing concern among occupational groups such as health care workers, first responders, sanitation workers, police and firemen that they may become infected with HIV through accidental needlesticks or splashes occurring at work. Nucleoside analogues such as Zidovudine (also referred to as AZT) are offered as prophylaxis to occupational groups following exposure to HIV contaminated materials. Use of dideoxynucleosides, such as ZDV, in healthy populations for prophylaxis has not been examined for potential reproductive or long term mutagenic effects. Such investigation is warranted given that genetic effects in humans and genetic plus reproductive effects in animals have been reported following ZDV exposure, and the data obtained would be of help to individuals and their physicians in making more informed risk/benefit decisions about the use of this type of prophylaxis following accidental occupational exposures. During the past year, fluorescence in situ hybridization (FISH) methods assessing aneuploidy in human sperm have been established at NIEHS. An IRTA summer student has also established methodology for enriching for round spermatids in human ejaculate. These methods will be used in proposed studies to be conducted through the NIEHS Clinical Centers contracts at Duke and/or UNC. A concept for proposed ZDV studies was presented to the Human Studies Faculty and a protocol incorporating their comments was prepared. The proposed study is a cohort study designed to compare individuals who are occupationally exposed to HIV and elect to take ZDV or other dideoxynucleoside prophylaxis therapy with occupationally exposed individuals who do not elect this prophylaxis therapy. Cytogenetic effects in blood lymphocytes and both fertility and cytogenetic parameters in sperm will be evaluated (repeated measure design). Subjects will be recruited from occupational exposures to HIV occuring in the greater Triangle area during a two year period and will be referred to the Clinical Research Study sites for specimen collection. Additionally, since a semen study is already underway at UNC with HIV infected individuals preparing to start didioxynucleoside therapy, coded aliquots of semen from these men will be obtained pre-, during, and post- dideoxynucleoside therapy. These specimens will be evaluated for cytogenetic and fertility effects as a second part to the ZDV Germ Cell Study.